Inhibition of DRP1 Impedes Zygotic Genome Activation and Preimplantation Development in Mice

Mitochondrion plays an indispensable role during preimplantation embryo development. Dynamic-related protein 1 (DRP1) is critical for mitochondrial fission and controls oocyte maturation. However, its role in preimplantation embryo development is still lacking. In this study, we demonstrate that inh...

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Autores principales:	Yuanyuan Li, Ning-Hua Mei, Gui-Ping Cheng, Jing Yang, Li-Quan Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	mitochondrial dysfunction preimplantation development zygotic genome activation ROS DRP1 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ef194160a06c460a917680c8670c1c4d
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spelling	oai:doaj.org-article:ef194160a06c460a917680c8670c1c4d2021-12-02T11:32:26ZInhibition of DRP1 Impedes Zygotic Genome Activation and Preimplantation Development in Mice2296-634X10.3389/fcell.2021.788512https://doaj.org/article/ef194160a06c460a917680c8670c1c4d2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.788512/fullhttps://doaj.org/toc/2296-634XMitochondrion plays an indispensable role during preimplantation embryo development. Dynamic-related protein 1 (DRP1) is critical for mitochondrial fission and controls oocyte maturation. However, its role in preimplantation embryo development is still lacking. In this study, we demonstrate that inhibition of DRP1 activity by mitochondrial division inhibitor-1, a small molecule reported to specifically inhibit DRP1 activity, can cause severe developmental arrest of preimplantation embryos in a dose-dependent manner in mice. Meanwhile, DRP1 inhibition resulted in mitochondrial dysfunction including decreased mitochondrial activity, loss of mitochondrial membrane potential, reduced mitochondrial copy number and inadequate ATP by disrupting both expression and activity of DRP1 and mitochondrial complex assembly, leading to excessive ROS production, severe DNA damage and cell cycle arrest at 2-cell embryo stage. Furthermore, reduced transcriptional and translational activity and altered histone modifications in DRP1-inhibited embryos contributed to impeded zygotic genome activation, which prevented early embryos from efficient development beyond 2-cell embryo stage. These results show that DRP1 inhibition has potential cytotoxic effects on mammalian reproduction, and DRP1 inhibitor should be used with caution when it is applied to treat diseases. Additionally, this study improves our understanding of the crosstalk between mitochondrial metabolism and zygotic genome activation.Yuanyuan LiNing-Hua MeiGui-Ping ChengJing YangLi-Quan ZhouFrontiers Media S.A.articlemitochondrial dysfunctionpreimplantation developmentzygotic genome activationROSDRP1Biology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mitochondrial dysfunction preimplantation development zygotic genome activation ROS DRP1 Biology (General) QH301-705.5
spellingShingle	mitochondrial dysfunction preimplantation development zygotic genome activation ROS DRP1 Biology (General) QH301-705.5 Yuanyuan Li Ning-Hua Mei Gui-Ping Cheng Jing Yang Li-Quan Zhou Inhibition of DRP1 Impedes Zygotic Genome Activation and Preimplantation Development in Mice
description	Mitochondrion plays an indispensable role during preimplantation embryo development. Dynamic-related protein 1 (DRP1) is critical for mitochondrial fission and controls oocyte maturation. However, its role in preimplantation embryo development is still lacking. In this study, we demonstrate that inhibition of DRP1 activity by mitochondrial division inhibitor-1, a small molecule reported to specifically inhibit DRP1 activity, can cause severe developmental arrest of preimplantation embryos in a dose-dependent manner in mice. Meanwhile, DRP1 inhibition resulted in mitochondrial dysfunction including decreased mitochondrial activity, loss of mitochondrial membrane potential, reduced mitochondrial copy number and inadequate ATP by disrupting both expression and activity of DRP1 and mitochondrial complex assembly, leading to excessive ROS production, severe DNA damage and cell cycle arrest at 2-cell embryo stage. Furthermore, reduced transcriptional and translational activity and altered histone modifications in DRP1-inhibited embryos contributed to impeded zygotic genome activation, which prevented early embryos from efficient development beyond 2-cell embryo stage. These results show that DRP1 inhibition has potential cytotoxic effects on mammalian reproduction, and DRP1 inhibitor should be used with caution when it is applied to treat diseases. Additionally, this study improves our understanding of the crosstalk between mitochondrial metabolism and zygotic genome activation.
format	article
author	Yuanyuan Li Ning-Hua Mei Gui-Ping Cheng Jing Yang Li-Quan Zhou
author_facet	Yuanyuan Li Ning-Hua Mei Gui-Ping Cheng Jing Yang Li-Quan Zhou
author_sort	Yuanyuan Li
title	Inhibition of DRP1 Impedes Zygotic Genome Activation and Preimplantation Development in Mice
title_short	Inhibition of DRP1 Impedes Zygotic Genome Activation and Preimplantation Development in Mice
title_full	Inhibition of DRP1 Impedes Zygotic Genome Activation and Preimplantation Development in Mice
title_fullStr	Inhibition of DRP1 Impedes Zygotic Genome Activation and Preimplantation Development in Mice
title_full_unstemmed	Inhibition of DRP1 Impedes Zygotic Genome Activation and Preimplantation Development in Mice
title_sort	inhibition of drp1 impedes zygotic genome activation and preimplantation development in mice
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ef194160a06c460a917680c8670c1c4d
work_keys_str_mv	AT yuanyuanli inhibitionofdrp1impedeszygoticgenomeactivationandpreimplantationdevelopmentinmice AT ninghuamei inhibitionofdrp1impedeszygoticgenomeactivationandpreimplantationdevelopmentinmice AT guipingcheng inhibitionofdrp1impedeszygoticgenomeactivationandpreimplantationdevelopmentinmice AT jingyang inhibitionofdrp1impedeszygoticgenomeactivationandpreimplantationdevelopmentinmice AT liquanzhou inhibitionofdrp1impedeszygoticgenomeactivationandpreimplantationdevelopmentinmice
_version_	1718395855481864192

Inhibition of DRP1 Impedes Zygotic Genome Activation and Preimplantation Development in Mice

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